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Metabolic adaptation of the renal carbohydrate metabolism. I. Effects of starvation on the gluconeogenic and glycolytic fluxes in the proximal and distal renal tubules

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Summary

The influence of starvation on renal carbohydrate metabolism was studied in the proximal and distal fragments of the nephron. Starvation induced a double and opposite adaptation mechanism in both fractions of the renal tubule. In renal proximal tubules, the gluconeogenic flux was stimulated progressively during a period of 48 hours of starvation (2.15 fold), due, in part, to a significant increase in the fructose 1,6-bisphosphatase and phosphoenolpyruvate carboxykinase activities although with different characteristics. Fructose 1,6-bisphosphatase activity from this tubular fragment increased only at subsaturating subtrate concentration (68%) which involved a significant decrease in the Km (35%) for fructose 1,6-bisphosphate while there was no change in Vmax. This behaviour clearly indicates that it is related to modifications in the activity of the preexistent enzyme in the cell. Proximal phosphoenolpyruvate carboxykinase activity increased proportionally at both substrate concentrations (86 and 89% respectively) which brought about changes in Vmax without changes in Kin, all of which are in accordance with variations in the cellular levels of the enzyme. In the renal distal tubules, the glycolytic capacity drastically decreased throughout the starvation time. At 48 hours 65% of inhibition was shown. We have found a short term regulation of phosphofructokinase activity by starvation which involves an increase in Km (2.2 fold) without changes in Vmax, as a result of these kinetic changes, an inactivation of phosphofructokinase was detected at subsaturating concentration of fructose 6-phosphate. On the contrary, this nutritional state did not modify the kinetic behaviour of renal pyruvate kinase. Finally, neither proximal glycolytic nor distal gluconeogenic capacities and related enzymes activities were changed during starvation.

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References

  1. Krebs HA, Bennett DAH, De Gasquet P, Gascoyne T, Yoshida T. Renal gluconeogenesis. The effect of diet on the gluconeogenic capacity of rat kidney cortex slices. Biochem J 86:22–27, 1963

    Google Scholar 

  2. Churchill PC, Belloni FL, Churchill MC: Net renal glucose release in rat. Am J Physiol 225:528–531, 1973

    Google Scholar 

  3. Kida K, Nakajo S, Kamiya F, Toyama Y, Nishio T, Nakagawa H: Renal net glucose release in vivo and its contribution to blood glucose in rats. J Clin Invest 62:721–726, 1978

    Google Scholar 

  4. Owen OE, Felig P, Morgan AP, Wahren J, Cahill CF Jr: Liver and kidney metabolism during prolonged starvation. J Clin Invest 48:574–583, 1969

    Google Scholar 

  5. Lupiáñez JA, Faus MJ, Muñoz-Clares R, Sánchez-Medina F: Stimulation of rat kidney gluconeogenesis ability by inhibition of liver gluconeogenesis. FEBS Lett. 61:277–281, 1976

    Google Scholar 

  6. Faus MJ, Lupiañez JA, Vargas A, Sánchez-Medina F: Induction of rat kidney gluconeogenesis during acute liver intoxication by carbon tetrachloride. Biochem J 174:461–468, 1978

    Google Scholar 

  7. Brinkman A, Katz N, Sasse D, Jungermann K: Increase of the gluconeogenic and decrease of the glycolytic capacity of rat liver with a change of the metabolic zonation after partial hepatectomy. Hoppe-Seyler's Z Physiol Chem 359:1561–1571, 1978

    Google Scholar 

  8. Sanchez-Pozo A, Lupiáñez JA, Corno A, Pita ML, Sánchez-Medina F: Differential effects of L-tryptophan administration on hepatic and renal gluconeogenesis in rats. Molecular Physiology 3:143–150, 1983

    Google Scholar 

  9. Iynedjian PB, Ballard FJ, Hanson RW: The regulation of phosphoenolpyruvate carboxykinase (GTP) synthesis in rat kidney cortex. The role of acid base balance and glucocorticoids. J Biol Chem 250:5596–5603, 1975

    Google Scholar 

  10. Pogson CI, Longshaw ID, Roobol A, Smith SH, Alleyne GAO: Phosphoenolpyruvate carboxykinase and renal gluconeogenesis. In: RW Hanson and MA Mehlman (eds) Gluconeogenesis. Its regulation in mammalian species. John Wiley and Sons, New York, pp 335–368, 1976

    Google Scholar 

  11. Cimbala MA, Lamers WH, Nelson K, Monahan JE, Yoo-Warren H, Hanson RW: Rapid changes in the concentration of phosphoenolpyruvate carboxykinase mRNA in rat liver and kidney effects of insulin and cyclic AMP. J Biol Chem 257:7629–7636, 1982

    Google Scholar 

  12. Guder WG, Ross BD: Enzyme distribution along the nephron. Kidney Int 26:101–111, 1984

    Google Scholar 

  13. Vinay P, Gougoux A, Lemieux G: Isolation of a pure suspension of rat proximal tubules. Am J Physiol 241:17403–17411, 1981

    Google Scholar 

  14. Mendicino J, Vasarhely F: Renal D-fructose 1,6-diphosphatase. J Biol Chem 238:3528–3534, 1963

    Google Scholar 

  15. Ballard FJ, Hansen RW: Phosphoenolpyruvate carboxykinase and pyruvate carboxylase in developing rat liver. Biochem J 104:866–871, 1967

    Google Scholar 

  16. Castaño TG, Nieto A, Feliu JE: Inactivation of phosphofructokinase by glucagon in rat hepatocytes. J Biol Chem 254:5576–5579, 1979

    Google Scholar 

  17. Carbonell J, Feliu JE, Marco R, Sols A: Pyruvate kinase classes of regulatory isoenzymes in mammalian tissues. Eur J Biochem 37:148–150, 1973

    Google Scholar 

  18. Lowry OH, Rosebrough NJ, Farr JL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275, 1951

    CAS  PubMed  Google Scholar 

  19. Bradford M: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254, 1976

    Article  CAS  PubMed  Google Scholar 

  20. Bergmeyer HU, Bernt E: Determination with glucose oxidase and peroxidase. In: HU Bergmeyer (ed) Methods of Enzymatic Analysis. Verlag Chemie Academic Press Inc, London and New York, pp 1205–1212, 1974

    Google Scholar 

  21. Gawehn K, Bergmeyer HU: L-(+)-lactate. Determination with lactate dehydrogenase and NAD. In: HU Bergmeyer (ed) Methods of Enzymatic Analysis. Verlag Chemie Academic Press Inc, London and New York, pp 1492–1495, 1974

    Google Scholar 

  22. Czok R, Lamprecht W. Pyruvate, phosphoenolpyruvate and D-glycerate-2-phosphate. In: HU Bergmeyer (ed) Methods of Enzymatic Analysis. Verlag Chemie Academic Press Inc, London and New York, pp 1446–1451, 1974

    Google Scholar 

  23. Azzout B, Peret J: Development of gluconeogenesis from dihydroxyacetone in rat hepatocytes during a feeding cycle and starvation. Biochem J 218:975–981, 1984

    Google Scholar 

  24. Atkins GL, Nimmo LA: A comparison of seven methods for fitting the Michaelis-Menten equation. Biochem J 149:775–777, 1975

    Google Scholar 

  25. Ross BD, Espinal J, Silva P: Glucose metabolism in renal tubular function. Kidney Int 29:54–67, 1986

    Google Scholar 

  26. Klein KL, Wang MS, Torikai S, Davidson WD, Kurokawa K: Substrate oxidation by isolated single nephron segments of the rat. Kidney Int 20:29–35, 1981

    Google Scholar 

  27. Heitmann RN, Bergman EN: Glutamate interconversions and glucogenicity in the sheep. Am J Physiol 241:E465-E472, 1981

    Google Scholar 

  28. Moore RE, Hansen JB, Lardy HA, Veneziale CM: The development and application of a radioimmunoassay for rat phosphoenolpyruvate carboxykinase. J Biol Chem 257:12546–12552, 1982

    Google Scholar 

  29. Dunaway GA: A review of animal phosphofructokinase isozymes with an emphasis on their physiological role. Mol Cell Biochem 52:75–91, 1983

    Google Scholar 

  30. Schering B, Reinacher M, Schoner W: Localization and role of pyruvate kinase isoenzymes in the regulation of carbohydrate metabolism and pyruvate recycling in rat kidney cortex. Biochim Biophys Acta 881:62–71, 1986

    Google Scholar 

  31. Krebs HA, Eggleston LV: The role of pyruvate kinase in the regulation of gluconeogenesis. Biochem J 94:3C-4C, 1965

    Google Scholar 

  32. Poole GP, Bloxham DP: The turnover of L-type pyruvate kinase in cultured rat hepatocytes. Biochem J 204:89–95, 1982

    Google Scholar 

  33. Van Berkel TIC, Kruijt JK, Van den Berg GB, Koster JF: Difference in the effect of glucagon and starvation upon L type pyruvate kinase from rat liver. Eur J Biochem 92:553–561, 1978

    Google Scholar 

  34. Kohl EA, Cottam GL: Alteration in liver pyruvate kinase protein and catalytic activity upon starvation and refeeding. Arch Biochem Biophys 176:671–682, 1976

    Google Scholar 

  35. Cimbala MA, Lau D, Daigneault JF: Starvation and feeding with a high-carbohydrate diet induce changes in the specific activity of rat hepatic pyruvate kinase. Biochem J 226:299–303, 1985

    Google Scholar 

  36. Ferré P, Pégorier JP, Williamson DH, Girard J: Interactions in vivo between oxidation of non-esterified fatty acids and gluconeogenesis in the newborn rat. Biochem J 182:593–598, 1979

    Google Scholar 

  37. Denton RM, Halestrap AP: Regulation of pyruvate metabolism in mammalian tissues. Essays Biochem 15:37–77, 1979

    Google Scholar 

  38. Marliss EB, Aoki TT, Unger RH, Soeldner JS, Cahill GF Jr: Glucagon levels and metabolic effects in fasting man. J Clin Invest 49:2256–2270, 1970

    Google Scholar 

  39. Silva P, Ross B, Spokes K: Competition between sodium reabsorption and gluconeogenesis in kidneys of steroid-treated rats. Am J Physiol 238:17290–17295, 1980

    Google Scholar 

  40. Hue L, Blackmore P, Exton JH: Fructose 2,6-bisphosphate. Hormonal regulation and mechanism of its formation in liver J Biol Chem 256:8900–8903, 1981

    Google Scholar 

  41. Pilkis SJ, Chrisman TD, Burgress B, McGrane M, Colosia A, Pilkis J, Claus TH, El-Maghrabi MR: Rat hepatic 6phosphofructo-2-kinase/fructose 2,6-bisphosphatase: a unique bifunctional enzyme. Adv Enzyme Regul 21:147–173, 1983

    Google Scholar 

  42. Van-Schaftingen E, Hers HG: Inhibition of fructose 1,6-bisphosphatase by fructose 2,6-bisphosphate. Proc Natl Acad Sci USA 78:2861–2863, 1981

    Google Scholar 

  43. Uyeda K, Furuya E, Sherry AD: The structure of ‘activation factor’ for phosphofructokinase. J Biol Chem 256:8679–8684, 1981

    Google Scholar 

  44. Brosnan JT, McPhee P, Hall B, Parry DM: Renal glutamine metabolism in rats fed high-protein diets. Am J Physiol 235:E261-E265, 1978

    Google Scholar 

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García-Salguero, L., Lupiáñez, J.A. Metabolic adaptation of the renal carbohydrate metabolism. I. Effects of starvation on the gluconeogenic and glycolytic fluxes in the proximal and distal renal tubules. Mol Cell Biochem 83, 167–178 (1988). https://doi.org/10.1007/BF00226144

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